Effects of rTMS Compared to SSRI as Early Treatment of Depression (Early-TMS)

Not Applicable

Not yet recruiting

• Conditions: Major Depressive Disorder
• Interventions: Drug: SSRI treatment; Device: bilateral theta burst stimulation

• Registration Number: NCT06545474
• Lead Sponsor: University Hospital Tuebingen

Brief Summary

The aim of this randomized multicentre phase 2 clinical trial is to compare the effects of rTMS and SSRI medication as early treatment of depression. In this two-stage, therapy response-adapted trial, 106 patients suffering from non-treatment resistant major depression (non-TR MD) will be randomized in Stage I to either 4 weeks bilateral theta burst stimulation (TBS) or 4 weeks antidepressant SSRI medication. The allocation to Stage II occurs therapy response-adapted. Patients receive either a maintenance treatment or a switch to the respective other treatment arm. The primary outcome is the comparison of the two study arms with regard to therapy response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) after 4 weeks at the end of Stage I.

Detailed Description

This is a therapy response-adapted, two-phase, randomized and controlled study. Initially, the study participants will be randomized to two treatment arms (Stage I: 4 weeks TBS vs. SSRI). After completion of Stage I, the allocation to Stage II (4 weeks) occurs therapy response-adapted. The type of further treatment depends on whether a remission, a treatment response or non-response has occurred in Stage I. If remission has been achieved, the treatment form already applied is continued as maintenance therapy. In the case of non-response, a switch to the other treatment arm takes place. For patients who show a treatment response but have not achieved remission, the corresponding patient preference is given special consideration for Stage II and thus determines the type of further treatment. Depending on patient preference, it is therefore possible both to continue treatment from Stage I and to switch to the other treatment arm.

The study aims to answer the question of whether a 4-week bilateral TBS is not inferior to standard antidepressant treatment with an SSRI in drug-naïve patients with MD in terms of efficacy and tolerability.

Study Timeline

• Status Verified: 2024-08
• Study First Submitted: 2024-08-05
• Study First Submitted QC: 2024-08-05
• Study First Posted: 2024-08-09
• Last Update Submitted: 2024-08-15
• Last Update Posted: 2024-08-19
• Study Start: 2024-09-15
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 106

Inclusion Criteria

• male, female, or diverse gender;
• age between 18 and 65 years;
• moderate to severe MD according to the diagnostic criteria of DSM-5;
• MADRS Score ≥ 20 points;
• the duration of the episode must be at least 2 weeks and not exceed a period of 2 years;
• no previous antidepressant treatment; indication for antidepressant medication;
• patients must be capable of giving informed consent.

Exclusion Criteria

• acute suicidal ideation (MADRS item 10 score > 4);
• presence of psychotic symptoms;
• antiepileptic drugs or benzodiazepines in a dosage equivalent to > 1 mg Lorazepam/d;
• comorbid Axis I disorder (except anxiety disorders);
• presence of severe, clinically relevant, and predominant comorbid personality disorder;
• treatment resistance defined as the failure of at least one adequate antidepressant treatment attempt in the current or previous depressive episode;
• neurological pre-existing conditions such as severe traumatic brain injury, neoplasms, brain surgery, stroke within the last 3 months, neurodegenerative diseases: epilepsy or history of epileptic seizures;
• cardiac pacemaker (not compatible with MRI);
• intracranial metallic implants;
• previous rTMS treatment;
• deep brain stimulation;
• other severe somatic diseases; pregnancy;
• contraindications for the use of escitalopram.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SSRI treatment	SSRI treatment	In Stage I, participants receive escitalopram (10mg/day) as standard medication for 4 weeks. In justified individual cases and according to the decision of the study physician, a higher dose or another SSRI can be administered.
theta burst stimulation (TBS)	bilateral theta burst stimulation	In Stage I, participants receive 4-week bilateral theta burst stimulation. Bilateral TBS consists of 20 sessions that are conducted daily from Monday to Friday over a period of 4 weeks. The target regions are the right and left dorsolateral prefrontal cortex (dlPFC). On the left hemisphere, intermittent TBS (iTBS) is applied, which has a stimulating effect on the target region similar to 10 Hz rTMS. On the right dlPFC, continuous TBS (cTBS) is applied, which has an inhibitory effect similar to 1 Hz rTMS.

Primary Outcome Measures

Name	Time	Method
response rates after Stage I	4 weeks	The primary endpoint is the comparison of the two study arms with regard to the number of participants achieving therapy response (reduction of MADRS score ≥ 50%) after 4 weeks at the end of Stage I.